Research conducted to date under the Statistics Core has yielded two provisional indexes having discriminant and predictive validity. The Transmissible Liability Index (TLI) and Non-Transmissible Liability Index (NTLl), evaluating the two sources of variance in SUD risk, independently predict diagnosis of cannabis used disorder between ages 10-12 and 22 (TLI OR=2.3;NTLl OR=2.8). Together they predict cannabis use disorder with 75% overall accuracy. These preliminary findings demonstrate the capacity to predict SUD consequent to use of illegal drugs up to 12 years after assessment. Accordingly, the research proposed in the new Translation Module has two overarching objectives. First will be cross-validation of the indexes by rederivation of the indexes using the sample of the Collaborative Studies on the Genetics of Alcoholism [COGA] as well as testing, clarifying, and adjusting for differences between genders, ethnicities, and the samples of the CEDAR and COGA studies. Preliminary correlation between the CEDAR-derived TLI and COGA-derived TLI equaled .98 (the CEDAR TLI had an alpha internal consistency of .74 in the COGA sample), suggesting good generalizability, of the TLI between samples. Cross-validation research will include joining the two indexes for quantification of SUD risk and traditional validity testing. As part of ongoing longitudinal research at CEDAR, this project establishes the foundation to apply etiology findings for selective/indicated SUD prevention. The TLI and NTLl, and their joining into a Resultant Liability Index (RLl), will enable accurate tracking of risk status from late childhood onward for elucidating SUD etiology within an ontogenetic framework. A second main objective of this project is to explicate the factors which intermediate (i.e., mediate or moderate) the relationship between the TLI or NTLl and SUD. To date, over 80 individual and environment latent constructs;that predict cannabis use disorder between childhood and adolescence, and/or discriminate high and low risk youths, have been derived using CEDAR's dataset. In addition to these 80 summative constructs are the manifold observed measures of CEDAR participants (10,000+ items at baseline). Thus, commensurate with selective/indicated prevention, this project will enable accurate detection of high risk youths and will provide guidance for the risks that need to be improved in subsequent intervention, based on the salient intermediary factors empirically linked to SUD etiology. The proposed project will be performed on the CEDAR cohort consisting of 800 families that have been sequentially enrolled for prospective study since 1990. At this juncture, the majority of the sample is passing through the modal period of risk for SUD. Thus, it is opportune (within the Statistics Core) to delineate and scale the transmissible (TLI) and non-transmissible (NTLl) components of SUD liability. It is equally timely (within the Translation Module) to prepare these indexes for applied uses and to delineate the factors that intermediate the TLI and SUD and/or NTLl and SUD to guide prevention strategy. Upon achieving these goals, efficient population screening will be feasible so as to guide selective/indicated prevention.